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| Status |
Public on May 29, 2015 |
| Title |
DK003: FOXO target gene CTDSP2 inhibits cell cycle progression through regulation of p21-Cip1/Waf1 |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Activity of Forkhead box O (FOXO) transcription factors is inhibited by PI3K-PKB/Akt signalling to control a variety of cellular processes including cell cycle progression. Through comparative analysis of a number of microarray datasets, we identified a set of genes commonly regulated by FOXO and PI3K/PKB, which includes Carboxyl-Terminal Domain Small Phosphatase 2 (CTDSP2). We validated CTDSP2 as a genuine FOXO target gene and show that ectopic CTDSP2 can induce cell cycle arrest. We analysed transcriptional regulation after CTDSP2 expression and identified extensive regulation of genes involved in cell cycle progression, which depends on the phosphatase activity of CTDSP2. Most notably regulated genes are p21Cip1/Waf1 and E2F1, both implicated in S-phase entry. We show that p21Cip1/Waf1 is regulated by CTDSP2 in a p53-independent manner and that p21Cip1/Waf1 upregulation results in decreased cyclin/CDK2 and cyclin/CDK6 activity. Thus, we identify FOXO-dependent CTDSP2 regulation as a novel regulatory mechanism for inhibiting proliferation in the absence of growth factor/PI3K signalling.
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| Overall design |
DL23 cells, containing FoxO3.A3-ER, stimulated with 4OHT for 8 hrs were compared to unstimulated cells in a direct comparison on dual-channel spotted expression microarrays. 4 biological replicates each were used. RNA samples were isolated and dye-swaps were done on half of the samples.
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| Contributor(s) |
Kloet DE, Polderman PE, Eijkelenboom AE, Smits LM, van Triest MH, van den Berg MC, Groot Koerkamp MJ, van Leenen D, Lijnzaad P, Holstege FC, Burgering BM |
| Citation(s) |
25990325 |
| Submission date |
Jun 30, 2014 |
| Last update date |
May 30, 2015 |
| Contact name |
Marian Groot Koerkamp |
| Organization name |
Princess Maxima Center for Pediatric Oncology
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| Department |
Research
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| Lab |
Drostlab
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| Street address |
Heidelberglaan 25
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| City |
Utrecht |
| State/province |
Utrecht |
| ZIP/Postal code |
3584 CS |
| Country |
Netherlands |
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| Platforms (1) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE58987 |
FOXO target gene CTDSP2 inhibits cell cycle progression through regulation of p21-Cip1/Waf1 |
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| Relations |
| BioProject |
PRJNA254056 |
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